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Papers In Press, published online ahead of print May 9, 2006
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Huck Institute for Life Sciences; Dept. of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802
Corresponding Author: acr6{at}psu.edu
Vitamin A (VA) is stored in tissues predominantly as retinyl esters (RE), which provide substrate for production of bioactive retinoids. Retinoic acid (RA), a principal metabolite, has been shown to induce postnatal lung development. To better understand lung RE storage, we compared VA (given as retinyl palmitate), RA, and a nutrient-metabolite combination, VARA, given orally on postnatal days 5-7, for their ability to increase lung RE in neonatal rats. VARA increased lung RE significantly (approximately 14, 2.4, 2.1, and <1 nmol/g for VARA, VA, RA, and C, respectively, P<0.001); the increase by VARA was more than additive as compared to the effects of VA and RA alone. Lung histology and morphometry were unchanged. In a 6-hour metabolic study, providing [3H]retinol with VARA, compared to with VA or C, increased the uptake of newly absorbed 3H three-fold, indicating that VARA stimulated uptake of [3H] retinol and its retention as [3H]RE in neonatal lungs. After cessation of VARA, lung RE remained elevated 9 d afterwards, through the period of alveolar development. In conclusion, VARA, a 10:1 nutrient-metabolite combination, increased lung RE significantly compared to VA alone, and could be a promising therapeutic option for enhancing the delivery of VA to the lungs.
Revised on April 13, 2006
Accepted on May 9, 2006
Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats
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